3,5-difluoroaniline is a known chemical with varied uses. It is particularly useful as an intermediate in production of herbicidal and pharmaceutical compositions. One known method for the production of 3,5-difluoroaniline is by amination of 1-bromo-3,5-difluorobenzene. Known processes for the manufacture of 1-halo-3,5-dihalobenzenes, including 1-bromo-3,5-difluorobenzene are discussed, for example, in U.S. Pat. No. 5,157,169, which issued to Patton on Mar. 26, 1992, the contents of which are incorporated herein by reference.
However, the processes discussed in the patent to Patton have several drawbacks. One particular drawback is the production in those processes of a diazonium salt as an intermediate. Diazonium salts can be explosive, and thus a build-up of diazonium salt in a manufacturing process presents an increased potential danger in carrying out such a process. According to the Patton reference, 2-bromo-4,6-difluoroaniline is diazotized in an aqueous solution of hydrochloric acid to afford a solution of diazonium salt. The diazonium salt is subsequently reduced using hypophosphorous acid. Thus, this process includes an increased level of danger particularly after the diazotization of 2-bromo-4,6-difluoroaniline and before reduction thereof with hypophosphorous acid. Moreover, the use of hypophosphorous acid is particularly costly.
Also, as set forth in the Patton reference, because the bromination reaction is exothermic, when conducted in an aprotic solvent, the reaction must be controlled to temperatures of less than 30.degree. C. This necessitates cooling the reaction mixture with corresponding additional costs to the production process.
Another drawback to the process discussed in the Patton reference is the necessity of collecting and drying the 2-bromo-4,6-difluoroaniline hydrobromide salt after the bromination step and before diazotization. This step is time consuming, and thus, when the process is used on a commercial level, will result in significant additional costs in the production of a 1-bromo-3,5-difluorobenzene product. Moreover, producing 1-bromo-3,5-difluorobenzene in two distinct steps, separated by a drying step, requires additional equipment, at least inasmuch as two reaction vessels, as well as additional filtering and drying equipment, are required to practice the process.
Yet another disadvantage to that process is the yield. According the Patton reference, the process discussed therein results in a yield of 2-bromo-4,6-difluoroaniline of about 75% (mole basis).
In view of the significant commercial uses of 3,5-difluoroaniline, there has been substantial commercial research directed to identifying commercially acceptable, safe, inexpensive and efficient methods for manufacturing 3,5-difluoroaniline products in high yields. However, despite the commercial interest and substantial research to identify such processes, no process has been found in which high yields of 3,5-difluoroaniline are achieved by a generally safe, inexpensive process while minimizing separate steps to isolate intermediates.